Out of the 3 billion genetic letters that spell out the human genome, Yale scientists have found a handful that may have contributed to the evolutionary changes in human limbs that enabled us to manipulate tools and walk upright.

Out of the 3 billion genetic letters that spell out the human genome, Yale scientists have found a handful that may have contributed to the evolutionary changes in human limbs that enabled us to manipulate tools and walk upright.

Related Articles

Results from a comparative analysis of the human, chimpanzee, rhesus macaque and other genomes reported in the journal Science suggest our evolution may have been driven not only by sequence changes in genes, but by changes in areas of the genome once thought of as “junk DNA.”

Those changes activated genes in primordial thumb and big toe in a developing mouse embryo, the researchers found.

“Our study identifies a potential genetic contributor to fundamental morphological differences between humans and apes,” said James Noonan, Assistant Professor of Genetics in the Yale University School of Medicine and the senior author of the study.

Researchers have long suspected changes in gene expression contributed to human evolution, but this had been difficult to study until recently because most of the sequences that control genes had not been identified. In the last several years, scientists have discovered that non-coding regions of the genome, far from being junk, contain thousands of regulatory elements that act as genetic “switches” to turn genes on or off.

A rapidly evolving sequence from the human genome drives gene activity in the developing thumb, wrist and ankle of mouse embryos, suggesting the sequence may have contributed to key evolutionary changes in the human limbs that allowed us to walk upright and use tools.

An indication of their biological importance, many of these non-coding sequences have remained similar, or “conserved,” even across distantly related vertebrate species such as chickens and humans. Recent functional studies suggest some of these “conserved non-coding sequences” control the genes that direct human development.

In collaboration with scientists at Lawrence Berkeley National Laboratory in California, the Genome Institute of Singapore, and the Medical Research Council in the United Kingdom, Noonan searched the vast non-coding regions of the human genome to identify gene regulatory sequences whose function may have changed during the evolution of humans from our ape-like ancestors.

Noonan and his colleagues looked for sequences with more base pairs in humans than in other primates. The most rapidly evolving sequence they identified, termed HACNS1, is highly conserved among vertebrate species but has accumulated variations in 16 base pairs since the divergence of humans and chimpanzees some 6 million years ago. This was especially surprising, as the human and chimpanzee genomes are extremely similar overall, Noonan said.

Using mouse embryos, Noonan and his collaborators examined how HACNS1 and its related sequences in chimpanzee and rhesus monkey regulated gene expression during development. The human sequence activated genes in the developing mouse limbs, in contrast to the chimpanzee and rhesus sequences. Most intriguing for human evolution, the human sequence drove expression at the base of the primordial thumb in the forelimb and the great toe in the hind limb. The results provided tantalizing, but researchers say preliminary, evidence that the functional changes in HACNS1 may have contributed to adaptations in the human ankle, foot, thumb and wrist-- critical advantages that underlie the evolutionary success of our species.

However, Noonan stressed that it is still unknown whether HACNS1 causes changes in gene expression in human limb development or whether HACNS1 would create human-like limb development if introduced directly into the genome of a mouse.

“The long-term goal is to find many sequences like this and use the mouse to model their effects on the evolution of human development,” Noonan said.

National Institutes of Health and the U.S. Department of Energy funded the work.

Story Source:

The above story is based on materials provided by Yale University. Note: Materials may be edited for content and length.

More From ScienceDaily

More Health & Medicine News

Featured Research

Mar. 3, 2015 — New assays can detect malaria parasites in human blood at very low levels and might be helpful in the campaign to eradicate malaria, reports a new study. An international team led by Ingrid Felger, ... full story

Mar. 3, 2015 — Adults over the age of 30 only catch flu about twice a decade, a new study suggests. So, while it may feel like more, flu-like illness can be caused by many pathogens, making it difficult to assess ... full story

Mar. 3, 2015 — No significant change in home habits of smokers have been observed in the aftermath of a ban on smoking in public spaces, researchers report. Greater inspiration to kick the habit likely comes from ... full story

Mar. 3, 2015 — Heart function has been associated with the development of dementia and Alzheimer's disease through a new study. Participants with decreased heart function, measured by cardiac index, were two to ... full story

Mar. 3, 2015 — Children of recently separated or divorced families are likelier to drink sugar-sweetened beverages than children in families where the parents are married, putting them at higher risk for obesity ... full story

Mar. 3, 2015 — Gastric bypass and similar stomach-shrinking surgeries are a popular option for obese patients looking to lose weight or treat type 2 diabetes. While the surgeries have been linked to a decreased ... full story

Mar. 3, 2015 — Most people consume more salt than they need and therefore have a higher risk of heart disease and stroke, which are the two leading causes of death worldwide. But a new study reveals that dietary ... full story

Mar. 3, 2015 — Twice as many children born to mothers who took antibiotics during pregnancy were diagnosed with asthma by age 3 than children born to mothers who didn’t take prenatal antibiotics, a new study has ... full story

Mar. 3, 2015 — Although sedatives are often administered before surgery, a randomized trial finds that among patients undergoing elective surgery under general anesthesia, receiving the sedative lorazepam before ... full story

Featured Videos

Mom Triumphs Over Tragedy, Helps Other Families

AP (Mar. 3, 2015) — After her son, Dax, died from a rare form of leukemia, Julie Locke decided to give back to the doctors at St. Jude Children&apos;s Research Hospital who tried to save his life. She raised $1.6M to help other patients and their families. (March 3)
Video provided by AP

Looted and Leaking, South Sudan's Oil Wells Pose Health Risk

AFP (Mar. 3, 2015) — Thick black puddles and a looted, leaking ruin are all that remain of the Thar Jath oil treatment facility, once a crucial part of South Sudan&apos;s mainstay industry. Duration: 01:13
Video provided by AFP

Woman Convicted of Poisoning Son

AP (Mar. 3, 2015) — A woman who blogged for years about her son&apos;s constant health woes was convicted Monday of poisoning him to death by force-feeding heavy concentrations of sodium through his stomach tube. (March 3)
Video provided by AP

Related Stories

Jan. 20, 2015 — A new computational method has been developed to identify which letters in the human genome are functionally important. Their computer program, called fitCons, harnesses the power of evolution, ... full story

Nov. 18, 2014 — A promising new method for delivering drugs into aggressive tumors by exploiting a unique feature of tumors themselves has been developed by researchers. "This opens up a new pathway to gene ... full story

July 3, 2013 — Thousands of sequences that control genes are active in the developing human limb and may have driven the evolution of the human hand and foot, a comparative genomics study has ... full story

Sep. 5, 2012 — The massive Encyclopedia of DNA Elements (ENCODE) unveiled Sept. 5 reveals a human genome vastly more rich and complex than envisioned even a decade ago. In a key supporting paper published in the ... full story

Apr. 28, 2011 — The size and shape of the human cerebral cortex, an evolutionary marvel responsible for everything from Shakespeare's poetry to the atomic bomb, are largely influenced by mutations in a single ... full story

ScienceDaily features breaking news and videos about the latest discoveries in health, technology, the environment, and more -- from major news services and leading universities, scientific journals, and research organizations.